tetano
Editor, Senior Moderator
Sci Immunol. 2017 Feb;2(8). pii: eaag2152. doi: 10.1126/sciimmunol.aag2152. Epub 2017 Feb 17.
[h=1]Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells.[/h] Herati RS[SUP]1,[/SUP][SUP]2[/SUP], Muselman A[SUP]1,[/SUP][SUP]2[/SUP], Vella L[SUP]2,[/SUP][SUP]3[/SUP], Bengsch B[SUP]2,[/SUP][SUP]4[/SUP], Parkhouse K[SUP]5[/SUP], Del Alcazar D[SUP]1,[/SUP][SUP]2[/SUP], Kotzin J[SUP]2,[/SUP][SUP]4[/SUP], Doyle SA[SUP]6[/SUP], Tebas P[SUP]1[/SUP], Hensley SE[SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Su LF[SUP]1,[/SUP][SUP]2[/SUP], Schmader KE[SUP]6[/SUP], Wherry EJ[SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38. This subset expressed more Bcl-6, c-Maf, and IL-21 than other blood CD4 subsets. Influenza vaccination induced a strong response in the ICOS+CD38+ cTfh at day 7, and this population included hemagglutinin-specific cells by tetramer staining and antigen-stimulated Activation Induced Marker (AIM) expression. Moreover, TCRB sequencing identified a clonal response in ICOS+CD38+ cTfh that correlated strongly with the increased circulating ICOS+CD38+ cTfh frequency and the circulating plasmablast response. In subjects who received successive annual vaccinations, a recurrent oligoclonal response was identified in the ICOS+CD38+ cTfh subset at 7 days after every vaccination. These oligoclonal responses in ICOS+CD38+ cTfh after vaccination persisted in the ICOS-CD38- cTfh repertoire in subsequent years, suggesting clonal maintenance in a memory reservoir in the more-stable ICOS-CD38- cTfh subset. These data highlight the antigen-specificity, lineage relationships and memory properties of human cTfh responses to vaccination, providing new avenues for tracking and monitoring cTfh responses during infection and vaccination in humans.
PMID: 28620653 PMCID: PMC5469419 DOI: 10.1126/sciimmunol.aag2152
Free PMC Article
[h=1]Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells.[/h] Herati RS[SUP]1,[/SUP][SUP]2[/SUP], Muselman A[SUP]1,[/SUP][SUP]2[/SUP], Vella L[SUP]2,[/SUP][SUP]3[/SUP], Bengsch B[SUP]2,[/SUP][SUP]4[/SUP], Parkhouse K[SUP]5[/SUP], Del Alcazar D[SUP]1,[/SUP][SUP]2[/SUP], Kotzin J[SUP]2,[/SUP][SUP]4[/SUP], Doyle SA[SUP]6[/SUP], Tebas P[SUP]1[/SUP], Hensley SE[SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Su LF[SUP]1,[/SUP][SUP]2[/SUP], Schmader KE[SUP]6[/SUP], Wherry EJ[SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38. This subset expressed more Bcl-6, c-Maf, and IL-21 than other blood CD4 subsets. Influenza vaccination induced a strong response in the ICOS+CD38+ cTfh at day 7, and this population included hemagglutinin-specific cells by tetramer staining and antigen-stimulated Activation Induced Marker (AIM) expression. Moreover, TCRB sequencing identified a clonal response in ICOS+CD38+ cTfh that correlated strongly with the increased circulating ICOS+CD38+ cTfh frequency and the circulating plasmablast response. In subjects who received successive annual vaccinations, a recurrent oligoclonal response was identified in the ICOS+CD38+ cTfh subset at 7 days after every vaccination. These oligoclonal responses in ICOS+CD38+ cTfh after vaccination persisted in the ICOS-CD38- cTfh repertoire in subsequent years, suggesting clonal maintenance in a memory reservoir in the more-stable ICOS-CD38- cTfh subset. These data highlight the antigen-specificity, lineage relationships and memory properties of human cTfh responses to vaccination, providing new avenues for tracking and monitoring cTfh responses during infection and vaccination in humans.
PMID: 28620653 PMCID: PMC5469419 DOI: 10.1126/sciimmunol.aag2152
Free PMC Article